Question 5

College Answer

The definition of high volume haemofiltration and its potential role in Intensive Care patients is unclear.  Purported benefits include clearance of “bad” cytokines/mediators, with improvement in cardiovascular function and even mortality.  More aggressive dailysis may have some survival advantages (Ronco et al Lancet 2000).  Though, in this large prospective RCT, there was no further benefit demonstrated when increasing the ultrafiltration rate > 35ml/hr/kg (ie. approx 2000 mL/hr).

No adequately powered studies assessing other benefits, especially in those without renal failure have been published.  Additional risks of the use of higher volumes are largely centre dependent, but certainly include potential problems with fluid and electrolyte balance.

Discussion

Rimmele and Kellum have a nice article from 2012 summarising the key points of this practice.

The evidence base for high volume haemofiltration is also discussed in the Required Reading chapters.

By a certain sort of extension, one can relate this to the evidence base regarding the optimal dose of dialysis.

One should approach a "critically evaluate" question systematically.

Thus:

Rationale

• Proinflammatory mediators contribute to the pathogenesis of multi-organ system failure in systemic inflammatory states
• Modification of their activity should have a beneficial effect on the progression of MOSF
• Removal of such mediators from the circulation might be an effective means of decreasing their influence
• These proinflammatory molecules are largely water-soluble, which means they can be removed by CVVHDF.
• Ultrafiltration is the ideal means of removing such molecules because their size (5kDa-60kDa) makes them sub-optimal candidates for removal by countercurrent diffusion in dialysis.

Advantages

• Potential benefit in removing inflammatory mediators, thus decreasing the severity of MSOF
• High volume ultrafiltration decreases the intravascular concentration of these molecules rapidly, resulting in a rapid redistribution of these mediators from the interstitial fluid and into the intravascular compartment (from which they can be removed)
• Increasing the concentration gradient in this way should increase the rate of diffusional cytokine removal from infected tissues, leading to decreased leucocyte migratio into those tissues, and thus decreasing the inflammatory damage to those tissues
• Hemofiltration membranes also have some adsorptive properties, allowing the fixation of molecules of a size greater than the membrane cutoff.
• High ultrafiltration rates may increase the exposure of more membrane sites by increasing transmembrane pressure.

Disadvantages

• High ultrafiltration rates will also remove more of the "useful" middle molecules, including the following:
  • Anti-inflammatory mediators
  • Water-soluble vitamins
  • Amino-acids and other nutrients
• High ultrafiltration rates will also remove large volumes of fluid, requiring large volumes of replacement fluid: this can result in undesirably large changes in electrolyte concentration
• The exposure of cellular blood components to the filter membrane at high pressure may result in greater rates of hemolysis and platelet depletion
• High transmembrane pressures increase the risk of membrane rupture and circuit failure
• High-volume ultrafiltration by CVVHDF is highly labour-intensive in the crude physical sense (eg. a dialysis dose of 120ml/kg/hr equates to "8 litre exchanges" in a 70kg patient, which means the nurse looking after the patient has to carry 8 L of effluent away each hour, returning with 8 litres of prepared replacement fluid).

Evidence

• Small early cohort studies had demonstrated an improvement in survival and hemodynamic performance with doses around 100ml/kg/hr, in patients with sepsis, pancreatitis, and SIRS due to post-cardiac arrest global ischaemia.
• The IVOIRE study (2013) compared doses of 75ml/kg/hr with 35ml/kg/hr. They found no benefit in either primary or secondary otucomes, and were forced to conclude that this therapy "cannot be recommended for septic shock complicated by AKI".
• A recent (2014) meta-analysis of high volume hemofiltration in patients with sepsis-associated AKI identified four RCTs, finding no evidence of benefit in primary or secondary outcomes, and attributing a greater frequency of wild electrolyte derangement to the high-volume group.

Summary for practice

• The available evidence does not support the use of high volume hemofiltration in systemic inflammatory states.

Bellomo, Rinaldo, Ian Baldwin, and C. Ronco. "High-volume hemofiltration." (2004): 375-382.

 

Rimmelé, Thomas, and John A. Kellum. "High-volume hemofiltration in the intensive care unit: a blood purification therapy." Anesthesiology 116.6 (2012): 1377-1387.

 

Honore, P. M., J. Jamez, and M. Wauthier. "Very high volume hemofiltration: A comprehensive review." Proceedings from the International Symposium on Critical Care Nephrology (ISCCN). Melbourne, Australia, Australasian Medical Pub Co. 2001.This is not available even as an abstract, anywhere!

 

Clark, Edward, et al. "High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis." Critical Care 18.1 (2014): R7.

 

Joannes-Boyau, Olivier, et al. "High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial." Intensive care medicine 39.9 (2013): 1535-1546.

 

Laurent, Ivan, et al. "High-Volume Hemofiltration After Out-of-Hospital Cardiac ArrestA Randomized Study." Journal of the American College of Cardiology46.3 (2005): 432-437.

 

Wang, Hao, et al. "Clinical effects of continuous high volume hemofiltration on severe acute pancreatitis complicated with multiple organ dysfunction syndrome." World Journal of Gastroenterology 9.9 (2003): 2096-2099.

 

Honore, Patrick M., et al. "Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock." Critical care medicine 28.11 (2000): 3581-3587.